Irradiation induces cancer lung metastasis through activation of the cGAS-STING-CCL5 pathway in mesenchymal stromal cells.

ABSTRACT: Emerging evidence indicates that mesenchymal stromal cells (MSCs) have an important role in cancer metastasis. Although tumor microenvironment, which includes MSCs and immune cells, can be altered by ionizing radiation (IR), whether irradiation can promote metastasis through MSCs remains unclear. Using the lung colonization model of transplanted 4T1 breast cancer cells, we found an increased lung metastasis in mice exposed to ionizing radiation, even when the thorax was shielded during whole-body irradiation. This radiation-induced lung metastasis can be replicated using irradiated MSCs. cGAS-STING signaling pathway was found to be activated in MSCs, accompanied by upregulation of type I interferon-related genes, including chemokine CCL5. Disruption of cGAS-STING signaling in MSCs abolishe

SUBMITTER: Zheng Z 

PROVIDER: S-EPMC7206094 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature